Trodelvy (sacituzumab govitecan-hziy)

The analyses confirmed mild-to-moderate renal impairment, mild hepatic impairment, age, tumor type (based on limited data in non-breast cancer tumor types), baseline albumin level, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on the exposure of the three analytes across populations. These findings support that the SG dosing regimen of 10 mg/kg on Days 1 and 8 of 21-day cycles is adequate for patients with HR+/HER2- mBC.

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center

P2, N=593, Recruiting, Gilead Sciences | Trial completion date: Jan 2027 --> Dec 2028

These findings highlight the potential utility of molecular profiling of CSF as an early indicator of treatment response and an approach for identifying resistance mechanisms and optimal combination therapies.

This study reveals that TROP2 is widely expressed in cholangiocarcinoma. Moreover, it provides preclinical evidence for the potential of the use of sacituzumab govitecan as a novel therapeutic strategy in treating patients with cholangiocarcinoma.

TROP2 expression is prevalent in ACC, particularly in the ductal cell component of the non-solid tumors. The pre-clinical drug screening findings provide a biological rationale for exploring TROP2 as a therapeutic target in TROP2-expressing ACC.

P1/2, N=272, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Despite significant advances with agents such as trastuzumab emtansine, sacituzumab govitecan and trastuzumab deruxtecan, resistance mechanisms limit their efficacy. Despite these advances, challenges remain, notably in identifying biomarkers of response and defining the optimal therapeutic sequence to avoid cross-resistance. Ongoing research is aimed at refining the use of ADCs to maximize their efficacy and prolong the survival of breast cancer patients.

Primary prophylactic administration of G-CSF and loperamide resulted in a clinically relevant reduction of the incidence and severity of sacituzumab govitecan-related neutropenia and diarrhea. Gilead Sciences, S.L.U.

P=N/A, N=20, Recruiting, Peking University Cancer Hospital & Institute

P2, N=150, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

P1/2, N=60, Not yet recruiting, Yale University | Trial completion date: Nov 2028 --> Aug 2030 | Initiation date: May 2025 --> Aug 2025 | Trial primary completion date: Nov 2028 --> Aug 2030

P2, N=20, Recruiting, British Columbia Cancer Agency | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Mar 2025

Clinical trials proposing its application in locally advanced HER2-BC have also been included. Furthermore, clinical trials showcasing the combination of Sacituzumab govitecan with numerous therapeutic modalities improving patient survival and quality of life in metastatic disease have also been included in the text.

These studies provided evidence for the treatment of patients with stable BM using sacituzumab govitecan, pembrolizumab combined with chemotherapy, trastuzumab deruxtecan (T-DXd), nab-paclitaxel combined with cisplatin, and talazoparib. Furthermore, if brain tissue is available, HER2 IHC should also be tested in order to evaluate the status switch and to assess the therapeutic effectiveness of treatment with T-DXd. Further targeted agents are urgently needed in order to improve the survival of patients with TNBC and BM.

P1, N=145, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting

From the perspective of a U.S. payer, at a willingness-to-pay (WTP) threshold of $150,000 per QALY, both T-DXd and SG were unlikely to be cost-effective compared to chemotherapy for HR+ and HER2-low metastatic breast cancer patients who have previously undergone chemotherapy. However, relative to SG, T-DXd achieved greater QALYs without a significant increase in cost.

In a large dataset, T-DXd showed favorable activity for treating MBC, although outcomes for HER2-positive disease appeared worse than those observed in clinical trials. Prior SG treatment was associated with inferior outcomes with T-DXd, suggesting cross-resistance between these antibody-drug conjugates.

We examine the efficacy of targeted therapies against TROP2, in particular the use of sacituzumab govitecan (SG), and evaluate their clinical impact on the treatment of various cancers. Through recent studies and clinical trials, we analyze the clinical effects of TROP2-ADCs and explored the prospects for their application in different cancers, including combination therapies with other therapeutic approaches, studies of resistance mechanisms, and further exploration of TROP2 as a biomarker. This review aims to provide a concise overview of TROP2 applications in cancer therapy, emphasizing emerging trends and therapeutic strategies to provide direction for future research and clinical practice.

In this study, Trop-2 expression did not predict excellent response versus non-response to SG in patients with HER2-negative MBC. Low Trop-2 expression, as determined by percentage staining, was predictive of shorter PFS, although the same association was not observed using the H-score. A complete lack of Trop-2 expression may predict SG ineffective, which requires further investigation.

Antibodies known as Aembrolizumab, Atezolizumab, and Sacituzumab Govitecan-hziy have been approved by the FDA, and many are under investigation. The present review discusses the antigens with high expression in TNBC, their role in cancer development and progression, and the targeted therapies like antibodies, recombinant proteins, and antibody-drug conjugates (ADC).

This study reveals that TROP2 is widely expressed in cholangiocarcinoma. Moreover, it provides preclinical evidence for the potential of use of sacituzumab govitecan as a novel therapeutic strategy in treating cholangiocarcinoma patients.

SG significantly improved PROs versus chemotherapy for several subdomains of EORTC QLQ-C30 and EQ-5D-5L-VAS. The consistency of these results in the overall population and subgroups supports the generalizability of the meta-analytic evidence and reinforces the PRO benefits associated with SG versus chemotherapy.

In TNBC, ADCs such as sacituzumab govitecan and trastuzumab deruxtecan have improved progression-free survival in advanced cases. While ADCs have significantly advanced treatment options in TNBC, PDAC remains a difficult target due to its stroma-rich microenvironment and lack of high-density, tumor-specific antigens. This article emphasizes the need for tailor-made ADC designs to enhance results in various types of cancers and provides valuable insight into future advancements in precision oncology.

P=N/A, N=70, Active, not recruiting, Peking University Cancer Hospital & Institute

ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) target cytotoxic payloads with specificity, whereas PARPis like olaparib, rucaparib, niraparib, and talazoparib cause synthetic lethality in homologous recombination repair (HRR)-deficient tumors. Future directions include biomarker-driven patient selection, combination with immune checkpoint inhibitors, and advancement in next-generation ADCs. The synergistic potential of ADC-PARPi combinations provides a new avenue for overcoming TNBC resistance, enhancing treatment outcomes, and widening therapeutic strategies for this challenging disease.

P1/2, N=31, Not yet recruiting, M.D. Anderson Cancer Center

Typical ADCs include trastuzumab emtansine for HER2-positive breast cancer, sacituzumab govitecan for triple-negative breast cancer (TNBC), and trastuzumab deruxtecan (T-DXd) for HER2-positive breast cancer, gastric cancer, and HER2 mutation-positive non-small cell lung cancer. In this article, we discuss the major mechanisms of resistance to ADCs, classifying them into five categories: mechanisms related to 'target antigen,' 'decreased internalization,' 'lysosomal dysfunction,' and 'payload sensitivity' and other resistance mechanisms [Figure 1]. We also discuss the strategies for overcoming ADC resistance.

Pembrolizumab is currently the only PD-1 checkpoint inhibitor approved in the United States in combination with chemotherapy in the first-line setting and is an option for roughly 40% of patients with PD-L1 positive tumors. Antibody-drug conjugates have been an important advance in the treatment of advanced TNBC, although these drugs do not represent a TNBC-specific advance as both sacituzumab govitecan and trastuzumab deruxtecan have activity in breast tumors beyond TNBC. Thus, despite significant strides over the past decade, significant unmet clinical need persists, and novel therapeutics remain a pressing need for the treatment of advanced TNBC.

P1/2, N=106, Enrolling by invitation, Dana-Farber Cancer Institute | Active, not recruiting --> Enrolling by invitation | Phase classification: P1 --> P1/2 | N=24 --> 106

P2, N=44, Recruiting, IRCCS San Raffaele | Trial completion date: Jun 2023 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2025

Sequential ADC therapy with topoisomerase-1-inhibiting payloads is a viable treatment strategy in HER2-low MBC. These results have hypothesis-generating clinical and translational implications. Further studies are needed to better understand ADC cross-resistance as more of these agents enter our clinical armamentarium.

This is the first report of "real-world" data on promising antitumor efficacy of SG in a heavily pretreated oral cancer patient with Trop-2 overexpression. Consistent with the findings of the Basket TROPiCS-03 study, SG appears to be a promising novel therapy option for R/M HNSCC after failure of immunotherapy and chemotherapy, particularly in patients with Trop-2 overexpression.

P=N/A, N=51, Recruiting, Peking University Cancer Hospital & Institute

P3, N=603, Active, not recruiting, Gilead Sciences | Trial completion date: May 2025 --> Jan 2026

At its current price, T-DXd is not cost effective for HER2-low metastatic breast cancer. Price reductions can make this drug cost effective. Optimal value-based sequencing in this patient population uses a single antibody-drug conjugate rather than back-to-back conjugates.

CDK4/6 inhibitors, trastuzumab deruxtecan, and sacituzumab govitecan have all been shown to provide significant overall survival benefits compared to conventional chemotherapy. The speed at which studies are now being carried out has markedly increased, and conferences and specialist journals are now constant sources of new information. This review summarizes the most recent publications and conference presentations on the treatment of patients with advanced stage breast cancer.

Patients homozygous for the UGT1A1*28 allele are at significantly increased risk of developing serious adverse events. Despite the clear relationship between UGT1A1 polymorphisms and sacituzumab-govitecan toxicity, the review suggests that there is insufficient consensus on the need for systematic genetic screening. However, the findings indicate that such screening could be useful for identifying patients at risk and personalizing sacituzumab govitecan therapy.

In addition, for both ER+ and ER- metastatic breast cancer (MBC) with nonoverexpressed human epidermal growth factor receptor 2 (HER2), this review highlights pivotal trials investigating antibody-drug conjugates (ADCs)-including trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan-and the challenges related to control arm selection and crossover that may affect outcome interpretation. Finally, for patients with HER2-positive disease, the review explores first-line and maintenance strategies-including insights from landmark trials like CLEOPATRA and PATINA-and addresses the impact of brain metastases on sequencing decisions. By critically appraising current data and identifying gaps in biomarker-guided and sequencing-specific strategies, this review provides practical insights to inform clinical practice and optimize personalized treatment plans for patients with MBC.

The results provide a foundational framework for clinical decision-making, and highlight the importance of collaborative expert synthesis in forming practice guidelines. Future studies should focus on prospective SG trials to address the identified areas of uncertainty.

Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.

P2, N=31, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Apr 2025 --> Sep 2027